Impact of interleukin-6 blockade with tocilizumab on SARS-CoV-2 viral kinetics and antibody responses in patients with COVID-19: A prospective cohort study

Abstract

Background The virological and immunological effects of the immunomodulatory drugs used for COVID-19 remain unknown. We evaluated the impact of interleukin (IL)-6 blockade with tocilizumab on SARS-CoV-2 viral kinetics and the antibody response in patients with COVID-19. Methods Prospective cohort study in patients admitted with COVID-19. Serial nasopharyngeal and plasma samples were measured for SARS-CoV-2 RNA and S-IgG/N-IgG titers, respectively. Findings 138 patients with confirmed infection were included; 76 (55%) underwent IL-6 blockade. Median initial SOFA ( p = 0•016) and SARS-CoV-2 viral load ( p <0•001, Mann-Whitney-Wilcoxon test) were significantly higher among anti-IL-6 users. Patients under IL-6 blockade showed delayed viral clearance in the Kaplan-Meier curves (HR 0•35 [95%CI] [0•15–0•81], log-rank p = 0•014), but an adjusted propensity score matching model did not demonstrate a significant relationship of IL-6 blockade with viral clearance (HR 1•63 [0•35–7•7]). Cox regression showed an inverse association between SARS-CoV-2 RNA clearance and the initial viral load (HR 0•35 [0•11–0•89]). Patients under the IL-6 blocker showed shorter median time to seropositivity, higher peak antibody titers, and higher cumulative proportion of seropositivity in the Kaplan Meier curves (HR 3•1 [1•9–5] for S-IgG; and HR 3•0 [1•9–4•9] for N-IgG; log-rank p <0•001 for both). However, no significant differences between groups were found in either S-IgG (HR 1•56 [0•41–6•0]) nor N-IgG (HR 0•96 [0•26–3•5]) responses in an adjusted propensity score analysis. Interpretation Our results suggest that in patients infected with SARS-CoV-2, IL-6 blockade does not impair the viral specific antibody responses. Although a delayed viral clearance was observed, it was driven by a higher initial viral load. The study supports the safety of this therapy in patients with COVID-19. Funding Instituto de salud Carlos III (Spain).

Therapeutic interventions for COVID-19: a living overview of reviews

“…Based on six systematic reviews that assessed tocilizumab, this IL-6 blockade agent could be beneficial in the treatment of severely ill COVID-19 patients. These findings are in line with recent cohort studies that have suggested that the IL-6 blockade does not impair the specific antibody response against SARS-CoV-2 and may help reduce the risk of death among severely ill COVID-19 patients; 82 , 83 nonetheless, they warrant further investigation in sufficiently controlled trials.…”

Interleukin-8 as a Biomarker for Disease Prognosis of Coronavirus Disease-2019 Patients

“…Blocking antibodies or small molecules targeting IL-6 or its signal transduction pathways have been used in the clinical trials to treat COVID-19 patients ( 23 , 29 ). However, targeting IL-6 signal transduction pathways might be complicated as IL-6 activates both pro-inflammatory pathway through the soluble form of the IL-6 receptor, and anti-inflammatory pathway through the membrane-bound form of the IL-6 receptor ( 27 , 44 ). IL-8 is clearly a pro-inflammatory cytokine that may recruit neutrophils to the infected areas and has been associated with tissue damage.…”

Optimal use of tocilizumab for severe and critical COVID-19: a systematic review and meta-analysis

“…Nevertheless, hospital and ICU lengths of stay did not differ between tocilizumab and SOC [20][21][22][23][24][25][26]31,32,35,40,43 . Only one study (Eimer et al) showed that length of stay in hospital on tocilizumab was shorter than the SOC and it was able to shorten the duration of use of a ventilator.…”